One type of the naturally occurring compounds with broad therapeutic applications is quinone. Quinone compounds widely exist in microorganisms, plants and animals (Thomson R H Naturally Occurring Quinones IV: Recent Advances. Published by Springer, 1996). Quinone compounds are redox capable and exist in vivo in one or several chemical species. Coenzyme Q10 is one of a few quinone compounds with fully identified chemical species profile in vivo (Bhagavan H N, et al. Mitochondrion, 2007, 7S: S78-88). The circulating coenzyme Q10 in human is almost entirely in the form of hydroquinone and the conversion to hydroquinone of the orally administered ubiquinone (oxidized form of coenzyme Q10) occurs in the enterocytes prior to its lymphatic transport into circulation (Craft N E, et al. FASEB J. 2005, 19, A449; Bhagavan H N, et al. Int. J. Pharmaceut. 2007, 333: 112-117; Mohr D, et al. Redox Rep. 1999, 4: 79-87).
Approved anticancer quinone compounds include daunorubicin, doxorubicin, epirubicin, idarubicin, valrubicin, and mitomycin. Their anticancer activity is mainly attributed to their ability to inhibit DNA replication in cancer cells by directly damaging DNA or interacting with proteins involved in DNA replication. Naphthofuran quinones have also a variety of biological activities. Some of them have been shown to have anticancer and other activities. For example, several natural occurring naphtho[2,3-b]furan-4,9-diones with interesting biological activities have been isolated from plants (Rao M M, et al. J. Natural Products, 1982, 45: 600-604; Tisler M, “Heterocyclic Quinones in Advances in Heterocyclic Chemistry” Vol. 45, ed. Katritzky A R, Academic Press, London, 1989, 56-63), and their analogs have further been found to have cytotoxic activity (Ogawa M, et al. Bioscience, Biotechnology, and Biochemistry, 2006, 70: 1009-1012; US20060142271; WO2009036059; WO2009036099; WO2009036101).
As cancer is a leading cause of death worldwide, accounting for 13% of all deaths according to 2004 World Health Organization statistics, there remains a need for novel compounds as active pharmaceutical ingredient useful for more effective treatment of cancer.